Thymectomy in non-thymomatous MG patients on Prednisone

接受泼尼松治疗的非胸腺瘤型 MG 患者的胸腺切除术

• 批准号: 7503345
• 负责人: Camilla Buckley
• 金额: --
• 依托单位: UNIVERSITY OF OXFORD
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-24 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7503345
• 关键词: Acetylcholine; Address; Adjuvant; Adrenal Cortex Hormones; Adverse effects; Adverse event; Age; Ancillary Study; Antibodies; Appendix; Area; Area Under Curve; Autoimmune Diseases; Cataract; Categories; Cholinergic Receptors; Clinical; Clinical Trials; Cost Savings; Daily; Data; Dose; End Point; Ensure; Evaluation; Failure; Frequencies; Future; Gender; Health Personnel; Human Resources; Immunotherapeutic agent; Individual; International; Life; Literature; Measures; Monitor; Muscle; Myasthenia Gravis; Operative Surgical Procedures; Osteoporosis; Outcome; Outcome Measure; Pain; Patient Monitoring; Patients; Pharmaceutical Preparations; Population; Population Study; Prednisone; Protocols documentation; Quality of life; Questionnaires; Randomized; Randomized Controlled Clinical Trials; Research Design; Research Personnel; Role; Safety; Score; Serious Adverse Event; Subgroup; Symptoms; Thymectomy; Thymus Gland; Time; Toxic effect; Unnecessary Procedures; age group; base; blind; clinical efficacy; design; disability; dosage; experience; neuromuscular transmission; patient safety; programs; pyridostigmine; receptor; response

DESCRIPTION (provided by applicant): Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85% of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission and can cause severe, sometimes life-threatening, weakness. Thymectomy has been used world-wide to treat non-thymomatous MG, based on retrospective non-randomized studies. Prednisone (a corticosteroid) is also frequently used to treat MG. Both therapies are often employed together and both have adverse effects. Whether thymectomy benefits those who are also receiving prednisone is not known. To investigate the safety while comparing efficacy, we propose a multicenter, multiracial, international, single-blinded, 3-year duration clinical trial in which patients aged 18-60 years with generalized AchR-Ab positive non- thymomatous MG are randomized to receive extended transsternal thymectomy (ETTX) or no thymectomy. Both groups will receive prednisone administered by a 'blind' evaluator according to the same set protocol aimed at establishing the minimum dose needed to achieve and maintain Minimal Manifestation (MM) status. The primary endpoint will comprise response and toxicity using a composite measuring clinical course, short and long term toxicities based on: (a) clinical efficacy of therapy evaluated by the QMG weakness score (b) frequency of serious adverse events (c) the total dose of prednisone (Area under the Dose time Curve, AUDTC). A significant difference favoring ETTX would establish its clinical benefits in this patient population, and provide indirect evidence of the possible benefits of ETTX in patients not receiving prednisone medication. Conversely, failure to demonstrate a significant difference in the global or individual components of the primary endpoint would suggest that thymectomy is an unnecessary procedure in the population studied. Subgroup analysis may show whether benefits are confined to those who are prednisone naive at entry or in a particular age group. Thus the results will impact on current clinical practice.

描述（由申请人提供）：重症肌无力 (MG) 是一种涉及胸腺的自身免疫性疾病，其中 85% 的患者具有肌肉乙酰胆碱受体 (AchR-Ab) 抗体，该抗体会干扰神经肌肉传递，并可能导致严重的、有时危及生命的无力。根据回顾性非随机研究，胸腺切除术已在世界范围内用于治疗非胸腺瘤型重症肌无力。泼尼松（一种皮质类固醇）也经常用于治疗重症肌无力。这两种疗法经常一起使用，并且都有副作用。胸腺切除术是否有益于同时接受泼尼松治疗的患者尚不清楚。为了在比较疗效的同时研究安全性，我们提出了一项多中心、多种族、国际、单盲、为期 3 年的临床试验，其中年龄为 18-60 岁的全身 AchR-Ab 阳性非胸腺瘤型 MG 患者被随机分配接受扩大经胸骨胸腺切除术 (ETTX) 或不接受胸腺切除术。两组均将接受由“盲”评估员根据同一设定方案施用泼尼松，旨在确定实现和维持最小表现（MM）状态所需的最小剂量。主要终点将包括反应和毒性，使用综合测量临床过程、短期和长期毒性，基于：(a) 通过 QMG 弱点评分​​评估治疗的临床疗效 (b) 严重不良事件的频率 (c) 泼尼松的总剂量（剂量时间曲线下面积，AUDTC）。有利于 ETTX 的显着差异将确定其在该患者群体中的临床益处，并提供 ETTX 对未接受泼尼松药物治疗的患者可能获益的间接证据。相反，如果未能证明主要终点的整体或个体成分存在显着差异，则表明胸腺切除术在研究人群中是不必要的手术。亚组分析可能表明获益是否仅限于那些刚开始未使用过泼尼松的人或特定年龄组的人。因此，结果将影响当前的临床实践。